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Description of key information

Key, acute toxicity, limit test, rat, oral (gavage), OECD 401, GLP: LD50 > 2000 mg/kg bw

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records
Reference
Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
8 JUL 1996 - 12 SEP 1996
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Remarks:
The study was performed in compliance with the Good Laboratory Practice (GLP) regulations. The method followed that described in the OECD Guidelines for Testing of Chemicals (Adopted: 24 Feb 1987) No 401 "Acute Oral Toxicity".
Qualifier:
according to guideline
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Version / remarks:
before 2002
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Species: Rat, Wistar HsdCpb: WU, males (m) and females (f)
- Source: F. Winkelmann, 33178 Borchen
- Age at study initiation: 6 - 9 weeks
- Weight at study initiation: 174 (165 - 184) g
- Fasting period before study: Diet was withheld from 17 hours before until up to 4 hours after treatment.
- Housing: The rats were housed in an air-conditioned room of about 10 m2. The rats were kept separately in type III Makrolon cages (37.5 x 21cm, height 15 cm) placed on mobile racks. Conventional softwood granulate was used as the bedding. One day before treatment, and up to 24 hours after dosing, metal grids were placed above the softwood granulate. The cages and the metal grids had been machine-cleaned before the start of the experimental part. The bedding was changed two times per week. The softwood granulate was analytically checked by independent laboratories.
- Diet (e.g. ad libitum): ad libitum (the diet (Altromin Standard Diet Total Pathogen Free TPF(R) N 1324 (10 mm pellets) for Rat/Mouse maintenance, nitrosamine deficient) is checked periodically by independent laboratories by an independent laboratory approved by the Geman government. Analysis included qualitative and quantitative evaluation for heavy metals, aflatoxins, pesticides, and antibiotics.)
- Water (e.g. ad libitum): ad libitum (the drinking water was periodically analyzed according to the German regulations for human drinking water.)
- Acclimation period: 7 d

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 - 25
- Humidity (%): 39 - 75
- Photoperiod (hrs dark / hrs light): 12/12
Route of administration:
oral: gavage
Vehicle:
other: Methocel K4M Premium
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 100 g/L
- Amount of vehicle (if gavage): 20 mL/kg

MAXIMUM DOSE VOLUME APPLIED: 2 mL/100 g
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
5 (m) / 5 (f)
Control animals:
no
Details on study design:
- Duration of observation period following administration: 15 days
- Frequency of observations and weighing: Observations were done for at least 6 h after administration and then checked daily. All rats were weighed before treatment and on days 2, 4, 6, 8, 11, 13, 15 of the experimental part
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, organ alterations
Statistics:
The body weight development of each rat and group was determined. The group mean value was calculated for each measurement and printed on tables.
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
All rats survived the observation period.
Clinical signs:
No signs of intoxication occurred after treatment.
Body weight:
Body weight development of the treated rats was inconspicuous.
Gross pathology:
At necropsy no organ alterations were seen.
Other findings:
None
Interpretation of results:
GHS criteria not met
Remarks:
Criteria used for interpretation of results: EU
Conclusions:
For regulatory purposes, the median lethal dose (LD50) for males and females, can be declared as > 2000 mg/kg bw after an observation period of 15 days.
Executive summary:

The acute oral toxicity of the test item was determined in a limit test according to OECD 401 and following GLP.

Purpose

The purpose of this assay was to provide information on possible health hazards for the test material and serve as a rational basis for risk assessment to the potential of acute oral toxicity of the test item in human.

Study design

The test was performed according to the OECD TG 401 "Acute oral toxicity" as a limit test using a dose of 2000 mg/kg body weight. Directly before the administration the test material was prepared with aqueous Methocel K4M Premium solution as vehicle.

Results

No signs of toxicity were detected after treatment and all rats rats survived the observation period. The gross pathological examination revealed no organ alterations.

Conclusions

According to the results of this study, the median lethal dose (LD50) for male and female rats exceeds 2000 mg/kg bw.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
discriminating dose
Value:
2 000 mg/kg bw
Quality of whole database:
The key study was performed in compliance with the Good Laboratory Practice (GLP) regulations. The method followed is described in the OECD Guidelines for Testing of Chemicals No 401 "Acute Oral Toxicity". Therefore, the quality of the database is high.

Acute toxicity: via inhalation route

Endpoint conclusion
Endpoint conclusion:
no study available

Acute toxicity: via dermal route

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Acute toxicity - oral

Acute oral toxicity, OECD 401

The acute oral toxicity of the test item was determined in a limit test according to OECD 401 and following GLP.

Purpose

The purpose of this assay was to provide information on possible health hazards for the test material and serve as a rational basis for risk assessment to the potential of acute oral toxicity of the test item in human.

Study design

The test was performed according to the OECD TG 401 "Acute oral toxicity" as a limit test using a dose of 2000 mg/kg body weight. Directly before the administration the test material was prepared with aqueous Methocel K4M Premium solution as vehicle.

Results

No signs of toxicity were detected after treatment and all rats rats survived the observation period. The gross pathological examination revealed no organ alterations.

Conclusions

According to the results of this study, the median lethal dose (LD50) for male and female rats exceeds 2000 mg/kg bw.

Justification for classification or non-classification

Based on the results of the key study (LD 50 in rats > 2000 mg/kg bw), no classification for acute toxicity is triggered in accordance with Regulation (EC) No 1272/2008.